Acute Myeloid LeukemiaPhase 1NCT06191978
A Phase Ia/Ib Open-label, Multiple Dose, Study to Determine the Recommended Dose, Evaluate PKs, PDs, Safety, and Activity of Venetoclax in Combination With Oral Decitabine/Cedazuridine (ASTX727) in Pediatric Patients With Relapsed/Refractory Acute Myeloid Leukemia (AML)
A Phase 1 study testing ASTX727 and Venetoclax in people with Acute Myeloid Leukemia, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial summary
To find a recommended dose of ASTX727 (cedazuridine/decitabine) in combination with venetoclax for pediatric patients with relapsed AML. Read more about this study
- Who is it for?
- Ages 2 to 18 years
- Conditions the study is for
- Acute Myeloid Leukemia
- What is being tested?
- ASTX727 and Venetoclax
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteUnited States
- Study dates
- 7 Mar 2024to 31 Dec 2028
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Pediatric Participants with Relapsed/refractory AML by WHO criteria.
- Participants must have ≥ 5% blasts in the bone marrow as assessed by morphology or flow cytometry. However, if an adequate bone marrow sample cannot be obtained, participants may be enrolled if there is unequivocal evidence of leukemia with ≥ 5% blasts in the peripheral blood or an AML defining genetic abnormality as specified by the WHO 2022 criteria.
- Performance status: Lansky ≥ 50 for participants who are ≤ 16 years old and Karnofsky ≥ 50% for participants who are > 16 years old.
- Age ≥2 years of age and ≤18 years of age
- Able to swallow pills
- The following baseline laboratory data:
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- Total serum bilirubin ≤1.5 x upper limit of normal (ULN) for age, unless the increased value is likely attributed to disease involvement. Participants with known Gilbert's syndrome may have a total bilirubin up to ≤5 x ULN for age.
- Creatinine clearance (Schwartz-Formula) or radioisotope GFR ≥ 60ml/min/1.73 m2 or a serum creatinine based on age/sex as follows:
- Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) ≤3 x ULN; ≤5 x ULN in case of suspected leukemic liver involvement.
- Females of childbearing potential must have a negative serum or urine beta human chorionic gonadotropin (β-HCG) pregnancy test result within 14 days prior to the first dose of study drugs and must agree to use one of the following effective contraception methods during the study and for 6 months following the last dose of study drug. Effective methods of birth control include:
- Birth control pills, skin patches, shots, implants (placed under the skin by a health care provider) ii. Intrauterine devices (IUDs) iii. Condom or occlusive cap (diaphragm or cervical/vault caps) used with Spermicide iv. Abstinence e. Males, need to inform the doctor right away if the partner becomes pregnant or suspects pregnancy. While in this study and for 3 months after the last treatment the patient should not donate sperm for the purposes of reproduction. He will need to use a condom while in this study and for 3 months after the last treatment.
- At least one parents or LAR must provide signature of informed consent and there must be documentation of assent by the subject, as age appropriate, before completing any study-related procedures.
Who cannot join
- Concomitant other anti-cancer therapy and/or participation in any other investigational clinical trials except for hydroxyurea. Concurrent hydroxyurea use should be limited to the first 2 cycles of therapy only.
- History of another primary invasive malignancy that has not been definitively treated and is in remission. Participants with non-melanoma skin cancers or with carcinomas in situ are eligible regardless of the time from diagnosis (including concomitant diagnoses).
- Presence of clinically significant uncontrolled central nervous system (CNS) pathology such as epilepsy, childhood seizure, paresis, aphasia, stroke, severe brain injuries, organic brain syndrome, or psychosis.
- Evidence of active cerebral/meningeal disease. Participants may have history of CNS leukemic involvement if definitively treated with prior therapy and no evidence of active disease at the time of consent with at least 2 consecutive spinal fluid negative assessments for residual leukemia and negative imaging (imaging required only if previously showing evidence of CNS leukemia not otherwise documented by spinal fluid assessment).
- Participants with uncontrolled, active infections (viral, bacterial, or fungal) or other disease expected to interfere with the ability of the PI to assess the efficacy of the study drug. Infections controlled on concurrent anti-microbial agents are acceptable, and anti-microbial prophylaxis per institutional guidelines are acceptable.
- Known active hepatitis B (eg, HBsAg reactive), or hepatitis C (eg, HCV RNA [qualitative] is detected), or chronic hepatitis B or C infection or human immunodeficiency virus (HIV) infection in medical history (historical results within 6 months prior to informed consent is acceptable), with the following exceptions:
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- Those with a history of hepatitis with a negative polymerase chain reaction (either qualitative or quantitative) OR have documentation of stable disease with aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase and alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase <2.0×upper limit of normal (ULN) may be eligible for this study.
- Subjects with history of HIV who have an undetectable viral load for the prior 3 months, and who agree to maintain antiviral therapy, may be eligible for the study.
- Liver cirrhosis or other serious active liver disease or with suspected active alcohol abuse.
- Exclude participants with active GVHD and those on immunosuppressive drugs for treatment of GVHD. Require that participants be off calcineurin inhibitors for at least 4 weeks to be eligible.
- Prior chemotherapy/radiotherapy/investigational therapy within 2 weeks before the start of study drugs with the following exception:
- To reduce the circulating blast count or palliation: intravenous cytarabine, steroids or hydroxyurea. No washout necessary for these agents.
- Females who are pregnant or lactating.
- Male or female subjects of childbearing potential, unwilling to use an approved, effective means of contraception.
- Other severe, uncontrolled acute or chronic medical or psychiatric condition or laboratory abnormality that in the opinion of the Investigator may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and/or would make the participant inappropriate for enrollment into this study.
- Participants with acute promyelocytic leukemia, juvenile myelomonocytic leukemia, or bone marrow failure syndromes are not eligible.
- Known or suspected hypersensitivity to decitabine, cedazuridine, or venetoclax.
- Participants on concomitant medications known to be metabolized by CDA will need review of the medication and assessment of possible impact of avoiding dosing during the 24 hours prior to possible enrollment, at the time of cedazuridine exposure, and 24 hours following the last dose of oral decitabine/cedazuridine.
- Participants of adult age (= 18 years of age) who are cognitively impaired will not be eligible for this study.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
MD Anderson Cancer Center
Houston, Texas, 77030
Amber Gibson, DO, 713-745-8177, algibson2@mdanderson.org
Amber Gibson, DO
About this study
To find a recommended dose of ASTX727 (cedazuridine/decitabine) in combination with venetoclax for pediatric patients with relapsed AML.
Read the detailed description
Primary Objectives
- To determine the recommended dose of ASTX727 when given in combination with venetoclax in relapsed/refractory (R/R) pediatric participants with acute myeloid leukemia (AML).
- To evaluate and describe the toxicities of ASTX727 and venetoclax administered in R/R AML pediatric population.
- To characterize the pharmacokinetic (PK) and pharmacodynamic (PD) profile of ASTX727 alone and in combination with venetoclax in an R/R AML pediatric population.
Secondary Objectives
- To evaluate the potential for drug-drug interactions: effect of venetoclax on PK of ASTX727.
- To define preliminary efficacy of ASTX727 when given in combination with venetoclax in pediatric participants. Efficacy will be based on Best Overall Response (BOR), including complete remission (CR), CR with incomplete blood count recovery, CR with incomplete hematologic recovery), and partial remission, overall survival (OS), event-free survival (EFS), and duration of response (DOR) of pediatric participants treated with this combination.
Exploratory Objectives To quantify the number of pediatric participants transitioning to Hematopoietic stem cell transplant (HSCT), i.e., CR/CRi/CRh rate, HR.
To identify biological markers of response to venetoclax and/or its combination with ASTX727. These effects could be at the molecular, cellular, or cytogenetic level.
- Conditions
- Acute Myeloid Leukemia
- Being tested
- ASTX727, Venetoclax
- Medical subject headings
- Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ASTX727Drug
Also called Inqovi
Given by PO
VenetoclaxDrug
Also called ABT-199, GDC-0199
Given by PO
| Study group | Role | What they receive |
|---|---|---|
| ASTX727/venetoclax | Experimental | On Days 1-5 of Cycle 1, you will take ASTX727 by mouth with a glass of water. Participants must fast (not eat or drink anything but water, black coffee, or tea) for at least 2 hours before and for 2 hours after taking ASTX727. For 4 hours before dosing and 4 hours after dosing, participants should not take antacids or any other medicine that can change the amount of acid in your stomach.
Days 1-21 or 1-28 depending on dose level, of all cycles beginning with Cycle 2. The study doctor will tell participants which of these schedules participants will follow. Venetoclax should be taken with water and a meal at around the same time each day. Receives: Drug: ASTX727; Drug: Venetoclax |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0
Measured: Through study completion; an average of 1 year.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jan 2024
- Study start7 Mar 2024
- Primary completion31 Dec 2028 (estimated)
- Study completion31 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Myeloid LeukemiaStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Astex Pharmaceuticals, Inc.
- Responsible party
- Sponsor
- Investigators
- Amber Gibson, DO, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06191978
- Sponsor's protocol ID
- 2023-0661
- Other IDs
- NCI-2023-10826
- Status last verified
- Sep 2026
- First submitted
- 19 Dec 2023
- Last updated
- 4 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase Ia/Ib Open-label, Multiple Dose, Study to Determine the Recommended Dose, Evaluate PKs, PDs, Safety, and Activity of Venetoclax in Combination With Oral Decitabine/Cedazuridine (ASTX727) in Pediatric Patients With Relapsed/Refractory Acute Myeloid Leukemia (AML)
- ClinicalTrials.gov ID
- NCT06191978
- Acronym / sponsor ID
- 2023-0661
- Conditions
- Acute Myeloid Leukemia
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Collaborators
- Astex Pharmaceuticals, Inc.
- Study start
- 7 Mar 2024 (actual)
- Primary completion
- 31 Dec 2028 (estimated)
- Study completion
- 31 Dec 2028 (estimated)
- First posted
- 5 Jan 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To find a recommended dose of ASTX727 (cedazuridine/decitabine) in combination with venetoclax for pediatric patients with relapsed AML.
Detailed description
Primary Objectives
- To determine the recommended dose of ASTX727 when given in combination with venetoclax in relapsed/refractory (R/R) pediatric participants with acute myeloid leukemia (AML).
- To evaluate and describe the toxicities of ASTX727 and venetoclax administered in R/R AML pediatric population.
- To characterize the pharmacokinetic (PK) and pharmacodynamic (PD) profile of ASTX727 alone and in combination with venetoclax in an R/R AML pediatric population.
Secondary Objectives
- To evaluate the potential for drug-drug interactions: effect of venetoclax on PK of ASTX727.
- To define preliminary efficacy of ASTX727 when given in combination with venetoclax in pediatric participants. Efficacy will be based on Best Overall Response (BOR), including complete remission (CR), CR with incomplete blood count recovery, CR with incomplete hematologic recovery), and partial remission, overall survival (OS), event-free survival (EFS), and duration of response (DOR) of pediatric participants treated with this combination.
Exploratory Objectives To quantify the number of pediatric participants transitioning to Hematopoietic stem cell transplant (HSCT), i.e., CR/CRi/CRh rate, HR.
To identify biological markers of response to venetoclax and/or its combination with ASTX727. These effects could be at the molecular, cellular, or cytogenetic level.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| ASTX727/venetoclax | Experimental | Drug: ASTX727, Drug: VenetoclaxOn Days 1-5 of Cycle 1, you will take ASTX727 by mouth with a glass of water. Participants must fast (not eat or drink anything but water, black coffee, or tea) for at least 2 hours before and for 2 hours after taking ASTX727. For 4 hours before dosing and 4 hours after dosing, participants should not take antacids or any other medicine that can change the amount of acid in your stomach. Days 1-21 or 1-28 depending on dose level, of all cycles beginning with Cycle 2. The study doctor will tell participants which of these schedules participants will follow. Venetoclax should be taken with water and a meal at around the same time each day. |
Who may qualify
- Ages
- 2 to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (12 listed)
- Pediatric Participants with Relapsed/refractory AML by WHO criteria.
- Participants must have ≥ 5% blasts in the bone marrow as assessed by morphology or flow cytometry. However, if an adequate bone marrow sample cannot be obtained, participants may be enrolled if there is unequivocal evidence of leukemia with ≥ 5% blasts in the peripheral blood or an AML defining genetic abnormality as specified by the WHO 2022 criteria.
- Performance status: Lansky ≥ 50 for participants who are ≤ 16 years old and Karnofsky ≥ 50% for participants who are > 16 years old.
- Age ≥2 years of age and ≤18 years of age
- Able to swallow pills
Key exclusion criteria (19 listed)
- Concomitant other anti-cancer therapy and/or participation in any other investigational clinical trials except for hydroxyurea. Concurrent hydroxyurea use should be limited to the first 2 cycles of therapy only.
- History of another primary invasive malignancy that has not been definitively treated and is in remission. Participants with non-melanoma skin cancers or with carcinomas in situ are eligible regardless of the time from diagnosis (including concomitant diagnoses).
- Presence of clinically significant uncontrolled central nervous system (CNS) pathology such as epilepsy, childhood seizure, paresis, aphasia, stroke, severe brain injuries, organic brain syndrome, or psychosis.
- Evidence of active cerebral/meningeal disease. Participants may have history of CNS leukemic involvement if definitively treated with prior therapy and no evidence of active disease at the time of consent with at least 2 consecutive spinal fluid negative assessments for residual leukemia and negative imaging (imaging required only if previously showing evidence of CNS leukemia not otherwise documented by spinal fluid assessment).
- Participants with uncontrolled, active infections (viral, bacterial, or fungal) or other disease expected to interfere with the ability of the PI to assess the efficacy of the study drug. Infections controlled on concurrent anti-microbial agents are acceptable, and anti-microbial prophylaxis per institutional guidelines are acceptable.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ASTX727Also: InqoviGiven by PO | Drug | ASTX727/venetoclax |
| VenetoclaxAlso: ABT-199, GDC-0199Given by PO | Drug | ASTX727/venetoclax |
Primary outcome
Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0
Time frame: Through study completion; an average of 1 year.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Sep 2026.
- MD Anderson Cancer CenterLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Amber Gibson, DO principal investigator
M.D. Anderson Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing ASTX727 and Venetoclax in people with Acute Myeloid Leukemia, run by M.D. Anderson Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 4 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Amber Gibson, DO ((713) 745-8177, algibson2@mdanderson.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0 (time frame: Through study completion; an average of 1 year.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Sep 2026.